Oat β‐Glucan and Galactooligosaccharides Influence Gallstone Formation by Modulating the Gut Microbiota, Particularly Desulfovibrionales

ABSTRACT Cholesterol gallstone disease is a prevalent ailment of the digestive system, accumulating evidence indicates a significant association between gut flora and gallstone formation. In the present research, we found that oat β‐glucan promotes gallstone formation, whereas galactooligosaccharides exerted inhibitory effects. Notably, these opposing effects were neutralized upon co‐administration of both prebiotics. Further research demonstrated that both prebiotics act primarily through modulating the abundance of Desulfovibrionales. The metabolic product of Desulfovibrionales, H 2 S, can directly activate the hepatic farnesoid X receptor (FXR) and thereby suppress bile acid production via FXR‐SHP signaling. Additionally, H 2 S can increase secondary bile acid levels (DCA, LCA) by promoting intestinal 7α‐dehydroxylase function. These secondary bile acids further decrease bile acid production in the liver via the intestinal FXR‐FGF15 cascade. Moreover, the upregulated production of secondary bile acids also enhances bile hydrophobicity. Collectively, these effects induce biliary cholesterol overloading, and ultimately promote gallstone formation. Our findings elucidate the effect of oat β‐glucan and galactooligosaccharides on gallstone formation, and suggest that alterations in Desulfovibrionales abundance and its influence on hepatic FXR‐SHP and intestinal FXR‐FGF15 pathways may underlie the potential mechanisms.